Drug Development Research,
Год журнала:
2023,
Номер
84(8), С. 1624 - 1651
Опубликована: Сен. 11, 2023
Alzheimer's
disease
(AD)
is
a
progressive
age-related
neurodegenerative
brain
disorder,
which
leads
to
loss
of
memory
and
other
cognitive
dysfunction.
The
underlying
mechanisms
AD
pathogenesis
are
very
complex
still
not
fully
explored.
Cholinergic
neuronal
loss,
accumulation
amyloid
plaque,
metal
ions
dyshomeostasis,
tau
hyperphosphorylation,
oxidative
stress,
neuroinflammation,
mitochondrial
dysfunction
major
hallmarks
AD.
current
treatment
options
for
acetylcholinesterase
inhibitors
(donepezil,
rivastigmine,
galantamine)
NMDA
receptor
antagonists
(memantine).
These
FDA-approved
drugs
mainly
provide
symptomatic
relief
without
addressing
the
pathological
aspects
progression.
So,
there
an
urgent
need
novel
drug
development
that
only
addresses
basic
but
also
shows
neuroprotective
property.
Various
research
groups
across
globe
working
on
multifunctional
agents
amelioration
using
different
core
scaffolds
their
design,
carbamate
among
them.
Rivastigmine
was
first
investigated
management.
fragment,
scaffold
act
as
potential
inhibitor
acetylcholinesterase.
In
this
review,
we
summarize
last
10
years
conducted
modification
with
substituents
primarily
target
ChE
inhibition,
reduce
modulate
Aβ
aggregation.
Antioxidants,
Год журнала:
2021,
Номер
10(5), С. 700 - 700
Опубликована: Апрель 29, 2021
Background:
Life
expectancy
is
increasing
along
with
the
rising
prevalence
of
cognitive
disorders.
Among
factors
that
may
contribute
to
their
prevalence,
modifiable
risk
such
as
diet
be
primary
importance.
Unarguably,
plant-based
diets
rich
in
bioactive
compounds,
polyphenols,
showed
potential
decreasing
neurodegenerative
Therefore,
aim
present
study
investigate
whether
exposure
components
diets,
namely
phenolic
acids,
affect
status
older
Italian
adults.
Methods:
The
demographic,
lifestyle
and
dietary
habits
a
sample
individuals
living
southern
Italy
were
analyzed.
Dietary
intake
was
assessed
through
food
frequency
questionnaires
(FFQs).
Data
on
acids
content
foods
estimated
using
Phenol-Explorer
database.
Cognitive
evaluated
Short
Portable
Mental
Status
Questionnaire.
Multivariate
logistic
regression
analyses
used
assess
associations.
Results:
mean
346.6
mg/d.
After
adjustment
for
confounding
factors,
highest
quartile
total
acid
less
likely
have
impaired
(OR
=
0.36
(95%
CI:
0.14,
0.92));
similarly,
analysis
subclasses
beneficial
effect
toward
greater
hydroxycinnamic
0.35
0.13,
0.91)).
individual
only
higher
caffeic
inversely
associated
0.32
0.11,
0.93));
notably,
association
ferulic
significant
when
adjusting
background
characteristics,
not
adherence
Mediterranean
diet.
Conclusions:
This
revealed
intakes
significantly
cognition,
emphasizing
possible
role
prevention
Molecules,
Год журнала:
2021,
Номер
26(21), С. 6573 - 6573
Опубликована: Окт. 30, 2021
Alzheimer's
disease
(AD)
is
a
progressive
neurodegenerative
disorder
and
the
leading
cause
of
dementia
worldwide.
The
limited
pharmacological
approaches
based
on
cholinesterase
inhibitors
only
provide
symptomatic
relief
to
AD
patients.
Moreover,
adverse
side
effects
such
as
nausea,
vomiting,
loss
appetite,
muscle
cramps,
headaches
associated
with
these
drugs
numerous
clinical
trial
failures
present
substantial
limitations
use
medications
call
for
detailed
insight
heterogeneity
development
preventive
multifactorial
therapeutic
strategies
urgent
basis.
In
this
context,
we
herein
report
series
quinoline-thiosemicarbazone
hybrid
therapeutics
selective
potent
cholinesterases.
A
facile
multistep
synthetic
approach
was
utilized
generate
target
structures
bearing
multiple
sites
chemical
modifications
establishing
drug-receptor
interactions.
all
synthesized
compounds
were
fully
established
using
readily
available
spectroscopic
techniques
(FTIR,
1H-
13C-NMR).
vitro
inhibitory
results
revealed
compound
5b
promising
lead
inhibitor
an
IC50
value
0.12
±
0.02
μM,
5-fold
higher
potency
than
standard
drug
(galantamine;
=
0.62
0.01
μM).
synergistic
effect
electron-rich
(methoxy)
group
ethylmorpholine
moiety
in
conjugates
contributes
significantly
improving
inhibition
level.
Molecular
docking
analysis
various
vital
interactions
amino
acid
residues
reinforced
results.
Kinetics
experiments
competitive
mode
while
ADME
properties
favored
translation
identified
into
safe
candidates
pre-clinical
testing.
Collectively,
activity
data
from
key
physicochemical
merit
further
research
ensure
design
high-quality
disease.
Pharmaceutics,
Год журнала:
2022,
Номер
14(2), С. 235 - 235
Опубликована: Янв. 20, 2022
It
has
become
increasingly
apparent
that
defective
insulin
signaling
may
increase
the
risk
for
developing
Alzheimer’s
disease
(AD),
influence
neurodegeneration
through
promotion
of
amyloid
formation
or
by
increasing
inflammatory
responses
to
intraneuronal
β-amyloid.
Recent
work
demonstrated
hyperglycemia
is
linked
cognitive
decline,
with
elevated
levels
glucose
causing
oxidative
stress
in
vulnerable
tissues
such
as
brain.
The
ability
β-amyloid
peptide
form
β-sheet-rich
aggregates
and
induce
apoptosis
made
fibrils
a
leading
target
development
novel
pharmacotherapies
used
managing
treatment
neuropathological
conditions
AD-related
decline.
Additionally,
deposits
β-sheets
folded
amylin,
homeostasis
regulator,
are
also
present
diabetic
patients.
Thus,
therapeutic
compounds
capable
reducing
intracellular
protein
aggregation
models
neurodegenerative
disorders
prove
useful
ameliorating
type
2
diabetes
mellitus
symptoms.
Furthermore,
both
conditions,
AD,
characterized
chronic
accompanied
presence
dysregulated
biomarkers.
This
review
presents
current
evidence
describing
role
various
small
bioactive
molecules
known
ameliorate
amyloidosis
subsequent
effects
prevention
AD.
highlights
potential
efficacy
peptide–drug
conjugates
targeting
targets.
Neural Regeneration Research,
Год журнала:
2023,
Номер
18(10), С. 2127 - 2127
Опубликована: Янв. 1, 2023
Toxic
aggregated
amyloid-β
accumulation
is
a
key
pathogenic
event
in
Alzheimer's
disease.
Treatment
approaches
have
focused
on
the
suppression,
deferral,
or
dispersion
of
fibers
and
plaques.
Gene
therapy
has
evolved
as
potential
therapeutic
option
for
treating
disease,
owing
to
its
rapid
advancement
over
recent
decade.
Small
interfering
ribonucleic
acid
recently
garnered
considerable
attention
gene
ability
down-regulate
genes
with
high
sequence
specificity
an
almost
limitless
number
targets,
including
those
that
were
once
considered
undruggable.
However,
lackluster
cellular
uptake
destabilization
small
biological
environment
restrict
application,
necessitating
development
vector
can
safeguard
genetic
material
from
early
destruction
within
bloodstream
while
effectively
delivering
across
blood-brain
barrier.
Nanotechnology
emerged
possible
solution,
several
delivery
systems
utilizing
nanoparticles
been
shown
bypass
challenges
regarding
delivery.
By
reducing
enzymatic
breakdown
components,
nanomaterials
carriers
considerably
enhanced
efficiency
therapy.
Liposomes,
polymeric
nanoparticles,
magnetic
dendrimers,
micelles
are
examples
nanocarriers
designed,
each
own
set
features.
Furthermore,
advances
specific
neurotrophic
compounds
via
provided
promising
results
relation
augmenting
cognitive
abilities.
In
this
paper,
we
highlight
use
different
targeted
acid-mediated
silencing
platform
Endocrine Metabolic & Immune Disorders - Drug Targets,
Год журнала:
2024,
Номер
24(13), С. 1506 - 1517
Опубликована: Фев. 20, 2024
Backgrounds:
Postbiotics
produced
by
gut
microbiota
have
exhibited
diverse
pharmacological
activities.
Valeric
acid,
a
postbiotic
material
and
some
plant
species
like
valerian,
has
been
explored
to
Methods:
This
narrative
review
aims
summarise
the
beneficial
role
of
valeric
acid
for
different
health
conditions
along
with
its
underlying
mechanism.
In
order
get
ample
scientific
evidence,
various
databases
Science
Direct,
PubMed,
Scopus,
Google
Scholar
were
exhaustively
collect
relevant
information.
Collected
data
arranged
analyzed
reach
meaningful
conclusion
regarding
bioactivity
profiling
mechanism,
future
prospects.
Results:
belongs
short-chain
fatty
acids
(SCFAs)
compounds
acetate,
propionate,
butyrate,
pentanoic
(valeric)
hexanoic
(caproic)
acid.
identified
as
one
potent
histone
deacetylase
(HDAC)
inhibitors.
preclinical
in
-vitro
in-vivo
studies,
found
anti-cancer,
anti-diabetic,
antihypertensive,
anti-inflammatory,
immunomodulatory
activity
affects
molecular
pathways
diseases
Alzheimer’s,
Parkinson’s,
epilepsy.
Conclusion:
These
findings
highlight
potential
novel
therapeutic
agent
endocrine,
metabolic
immunity-related
conditions,
it
must
be
tested
under
clinical
develop
promising
drug.
Expert Opinion on Drug Delivery,
Год журнала:
2024,
Номер
21(3), С. 479 - 493
Опубликована: Март 3, 2024
Ferulic
acid
(FA)
is
a
phenolic
phytochemical
that
has
garnered
the
attention
of
research
community
due
to
its
abundant
availability
in
nature.
It
compound
been
explored
for
multifaceted
therapeutic
potential
and
benefits
modern
contemporary
healthcare.
Chemical Biology & Drug Design,
Год журнала:
2024,
Номер
104(4)
Опубликована: Окт. 1, 2024
ABSTRACT
Alzheimer's
disease
(AD)
is
a
chronic
progressive,
age‐related
neurodegenerative
brain
disorder
characterized
by
the
irreversible
decline
of
memory
and
other
cognitive
functions.
It
one
major
health
threat
21st
century,
which
affects
around
60%
population
over
age
60
years.
The
problem
this
even
more
because
existing
pharmacotherapies
only
provide
symptomatic
relief
without
addressing
basic
factors
disease.
extracellular
deposition
amyloid
β
(Aβ)
to
form
senile
plaques,
intracellular
hyperphosphorylation
tau
neurofibrillary
tangles
(NFTs).
Due
complex
pathophysiology
disease,
various
hypotheses
have
been
proposed,
including
cholinergic,
Aβ,
tau,
oxidative
stress,
metal–ion
hypothesis.
Among
these,
cholinergic
Aβ
are
primary
targets
for
AD.
Therefore,
continuous
advances
made
in
developing
potential
cholinesterase
inhibitors
N
‐methyl‐D‐aspartate
(NMDA)
receptor
antagonists
delay
progression
restore
neurotransmission.
In
review
article,
we
tried
comprehensively
summarize
recent
advancement
NMDA
antagonist
(memantine)
their
hybrid
analogs
as
disease‐modifying
agents
treatment
Furthermore,
also
depicted
design,
rationale,
SAR
analysis
memantine‐based
hybrids
used
last
decade
